Combination Therapy for Advanced Breast Cancer
What You Need to Know Before You Apply
What is the purpose of this trial?
This trial explores a new combination of treatments for individuals with advanced HER2-negative breast cancer that has not responded to previous treatments. It involves using alpelisib with chemotherapy and L-NMMA (an experimental treatment) to assess their safety and effectiveness together. The study seeks participants with HER2-negative breast cancer that has spread or cannot be surgically removed and who have previously tried other treatments without success. Participants will receive the treatments every three weeks to determine if this new combination can better manage the disease. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to potentially benefit from a promising new therapy.
Will I have to stop taking my current medications?
The trial requires that you stop taking strong inhibitors or inducers of CYP3A4 at least 1 week before starting the study. If you are on warfarin or other coumarin-derived anticoagulants, you will need to switch to a different type of blood thinner. Other medications that interact with nitrate/nitrite levels are also not allowed.
Is there any evidence suggesting that this trial's treatments are likely to be safe?
Research is investigating the safety of combining three drugs—alpelisib, nab-paclitaxel, and L-NMMA—in patients with advanced breast cancer. Alpelisib, already approved for other cancers, may cause side effects like high blood sugar and diarrhea. Nab-paclitaxel, a chemotherapy drug, is generally well-tolerated but can lead to hair loss and low blood cell counts. L-NMMA is less common, and its side effects remain under study, though it has been used in other trials. As this is an early-stage study, researchers are closely monitoring for any side effects to ensure patient safety.12345
Why do researchers think this study treatment might be promising?
Researchers are excited about the combination of iNOS inhibitor and nab-paclitaxel with alpelisib for advanced breast cancer because it offers a unique approach compared to standard treatments like chemotherapy and targeted therapies. Most treatments for HER2-negative metastatic breast cancer focus on blocking hormone receptors or using traditional chemotherapy. However, this combination targets the iNOS pathway, which is believed to contribute to cancer progression, alongside inhibiting the PI3K pathway with alpelisib. This dual-action strategy could potentially offer more effective suppression of tumor growth and spread, providing new hope for patients with this aggressive form of cancer.
What evidence suggests that this trial's treatments could be effective for advanced breast cancer?
In this trial, participants will receive a combination of alpelisib, nab-paclitaxel, and L-NMMA to treat HER2 negative metastatic breast cancer. Research has shown that this combination might benefit patients by targeting specific pathways in cancer cells. Alpelisib targets PIK3CA, a part of cancer cells that often promotes growth. L-NMMA blocks the enzyme iNOS, which can also aid cancer growth. Together, these drugs aim to stop cancer cells from growing and spreading. Early studies suggest this combination might be more effective than chemotherapy alone. While more information is needed, initial results are promising for those who haven't responded to other treatments.12456
Who Is on the Research Team?
Polly Niravath, MD
Principal Investigator
Houston Methodist Cancer Center
Are You a Good Fit for This Trial?
This trial is for adults with HER2 negative metastatic or advanced metaplastic breast cancer that hasn't improved after previous treatments. Participants must be able to follow the study plan, have measurable disease, and acceptable organ function. Women of childbearing age and sexually active men must use contraception. Exclusions include certain drug interactions, uncontrolled hypertension, serious heart conditions, other active cancers, severe lung disease or neuropathy, pancreatitis, blood clotting disorders on specific anticoagulants, history of severe skin reactions or untreated brain metastases.Inclusion Criteria
Exclusion Criteria
Timeline for a Trial Participant
Screening
Participants are screened for eligibility to participate in the trial
Treatment
Participants receive alpelisib, L-NMMA, and nab-paclitaxel every 3 weeks until disease progression, toxicity, or withdrawal
Follow-up
Participants are monitored for safety and effectiveness after treatment
What Are the Treatments Tested in This Trial?
Interventions
- L-NMMA
Find a Clinic Near You
Who Is Running the Clinical Trial?
The Methodist Hospital Research Institute
Lead Sponsor
Novartis Pharmaceuticals
Industry Sponsor
Dr. Vas Narasimhan
Novartis Pharmaceuticals
Chief Executive Officer since 2018
MD from Harvard Medical School
Dr. Shreeram Aradhye
Novartis Pharmaceuticals
Chief Medical Officer since 2021
MD